文章：

表观遗传时钟与膀胱癌风险之间的显著关联

The Significant Associations between Epigenetic Clocks and Bladder Cancer Risks

原文发布日期：27 June 2024

DOI: 10.3390/cancers16132357

类型: Article

开放获取: 是

英文摘要：

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case–control study, we assessed the associations between four well-established epigenetic clocks—HannumAge, HorvathAge, GrimAge, and PhenoAge—and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for each clock. We discovered that higher HannumAge and HorvathAge GRS were significantly associated with increased bladder cancer risk (OR = 1.69 per SD increase, 95% CI, 1.44–1.98,p= 1.56 × 10−10and OR = 1.09 per SD increase, 95% CI, 1.00–1.19,p= 0.04, respectively). Employing a summary statistics-based Mendelian randomization (MR) method, inverse-variance weighting (IVW), we found consistent risk estimates for bladder cancer with both HannumAge and HorvathAge. Sensitivity analyses using weighted median analysis and MR-Egger regression further supported the validity of the IVW method. However, GrimAge and PhenoAge were not associated with bladder cancer risk. In conclusion, our data provide the first evidence that accelerated biological aging is associated with elevated bladder cancer risk.

摘要翻译： 

膀胱癌是一种与年龄相关的疾病，超过四分之三的病例发生在65岁及以上人群中。加速的生物衰老与癌症风险升高相关。表观遗传时钟是生物年龄的优良预测指标，但其是否与膀胱癌风险相关尚不明确。在这项大型病例对照研究中，我们评估了四种公认的表观遗传时钟——HannumAge、HorvathAge、GrimAge和PhenoAge——与膀胱癌风险的关联。利用全基因组关联研究（GWAS）中鉴定出的与这些时钟相关的单核苷酸多态性（SNPs）作为工具变量，我们为每个时钟构建了加权遗传风险评分（GRS）。我们发现，较高的HannumAge和HorvathAge GRS与膀胱癌风险增加显著相关（OR = 1.69每SD增加，95% CI，1.44–1.98，p = 1.56 × 10⁻¹⁰；OR = 1.09每SD增加，95% CI，1.00–1.19，p = 0.04）。采用基于汇总统计数据的孟德尔随机化（MR）方法——逆方差加权（IVW），我们发现HannumAge和HorvathAge与膀胱癌的风险估计结果一致。使用加权中位数分析和MR-Egger回归进行的敏感性分析进一步支持了IVW方法的有效性。然而，GrimAge和PhenoAge与膀胱癌风险无关。总之，我们的数据首次提供了证据，表明加速的生物衰老与膀胱癌风险升高相关。

原文链接：

The Significant Associations between Epigenetic Clocks and Bladder Cancer Risks